This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is designed to be an extensive effort to perform a genome-wide analysis and mapping of the possible genetic basis for the many aspects of COPD. It is the largest and most expensive COPD study ever funded by the NIH. Cigarette smoking is widely acknowledged to be the main cause of COPD. However, only a minority of all smokers will develop COPD. There are different types of lung disease that are grouped under the heading of COPD but have very different characteristics. People who develop emphysema have damaged alveoli and poor gas exchange. People who develop airway disease such as chronic bronchitis will have narrowed airways with inflammation and increased mucus production. It is not clear why some smokers might develop one form of the disease over the other forms. Genetic studies of complex diseases like COPD have the potential to provide insight into the mechanisms of COPD differences and susceptibility. A strong genetic basis for susceptiblility of smokers to develop COPD is suggested by marked variability in the development of airflow obstruction among smokers, clear familial clustering of COPD (and specific types of COPD), and linkage of specific types of COPD to specific genes or groups of genes in families with severe, early-onset COPD. This study will attempt a comprehensive genome-wide analysis to identify genes influencing COPD in two major racial/ethnic groups: non-Hispanic Caucasians and African-Americans. These two groups were carefully chosen;there is expected to be appreciable differences in genetic associations among ethnic groups and it was determined to be not feasible to study all ethnic groups in this initial study. All study subjects will have a history of smoking, but both those who have developed COPD and those who have not will be studied.